Concomitant trastuzumab with thoracic radiotherapy: a morphological and functional study

Yavaş, Güler; Yıldız, F.; Guler, Salih; Sargon, Mustafa F.; Yıldız, Demir Kürşat; Yolcu, T.; Tuncer, Meral; Akyol, Fadıl

doi:10.1093/annonc/mdq590

Cited by 14 publications

(25 citation statements)

References 32 publications

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“…Bese et al (20) reported that concomitant use of T with RT (12 Gy) or subsequent use did not increase pulmonary fibrosis in rats. In another animal study, it was found that concomitant use of T with high-dose RT (15 Gy) resulted in might lead to vascular damage that seemed at least additive damage on thoracic aorta (21). In both studies, T was administered in 6 mg/kg dose, in consistent with our study.…”

Section: Discussionsupporting

confidence: 86%

The effects of hormonotherapy administered concurrent radiotherapy and trastuzumab on cardiac toxicity in rats

Cihan¹,

Arsav²

2014

Anadolu Kardiyol Derg

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Objective: This experimental study aims to investigate whether radiotherapy (RT) plus trastuzumab (T) followed by subsequent hormonotherapy increase the cumulative toxic effect on cardiac functions in rats. Methods: A total of 70 Wistar-Albino female rats with a mean weight 213±27 g were randomly divided into equal seven groups. The first group (C) underwent no procedure. The second group (RT) underwent the whole thoracic radiation including heart. The third group (T) was administered T through tail vein alone. The fourth group (RT+T+Tx) was administered T initially and the whole thoracic radiation at two hours, followed by tamoxifen at one week. The fifth group (RT+T+Le) was administered T and then underwent thoracic radiation, followed by letrozole. The sixth group (T+RT+An) was administered T and then underwent thoracic radiation, followed by anastrazole. The seventh group (T+RT+Ex) was administered T and then underwent thoracic radiation, followed by exemestane at one week. Hormonotherapy was administered to the rats in the Group 5, 6 and 7, as indicated in the Group 4. Radiation therapy was administered following T treatment at two hours as a single 12 Gy fraction. After the rats were sedated under anesthesia and sacrificed at 24 weeks, cardiac tissues were removed. Serial sections obtained following paraffin blockage were stained and the ratio of myocardial fibrosis was assessed. According to statistical analyses by the one-way ANOVA test and Tukey HSD test, a significant difference between test components. Results: At the end of the study, no loss and adverse effects were seen in any group. There was a statistically significant difference among atrium, ventricle and aorta (p<0.001). The mean value of fibrosis scores increased in the rats which underwent RT. In the assessment of atrium, a significant difference was found between RT group and RT+T+An group and also T group and RT+T+Fe group (p<0.001). In the assessment of ventricule, a statistically significant difference was observed among RT, RT+T+An and RT+T+Ex. In the assessment of aorta, the scores of RT group was significantly higher than RT+T+An and RT+T+Ex. A statistically significant difference was observed among these groups (p<0.001). Conclusion: Our study results suggested that there was no significant additional cardiotoxicity of adjuvant hormonotherapy following concomitant RT and T treatment, compared to RT in terms of cardiac fibrosis. (Anadolu Kardiyol Derg 2014; 14: 328-33)

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Section: Discussionsupporting

confidence: 86%

The effects of hormonotherapy administered concurrent radiotherapy and trastuzumab on cardiac toxicity in rats

Cihan¹,

Arsav²

2014

Anadolu Kardiyol Derg

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“…9 The 8 Gy dose of RT was not enough to cause significant changes both from functional and morphological aspects. On the other hand 15 Gy RT led significant changes.…”

Section: Discussionmentioning

confidence: 97%

The effect of halofuginone on radiation-induced cardiovascular injury

Yavaş¹,

Çalık

Yavaş

et al. 2015

Int J Cancer Ther Oncol

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Purpose: The main purpose of this study was to evaluate the effects of Halofuginone on radiation-induced cardiovascular injury in a rat model. Methods: Sixty Wistar-Albino rats were divided into six groups (the control group, radiotherapy (RT) only group Irradiation (IR), 2.5 and 5 μg Halofuginone groups (Hal (2.5)/C and Hal (5.0)/C), and RT plus 2.5 and 5 μg Halofuginone groups (Hal (2.5)/IR and Hal (5.0)/IR). Rats were exposed to a single dose of 12 Gy irradiation generated by a linear accelerator. Halofuginone was applied intraperitoneally with daily doses. At the 6 th and 16 th weeks of RT, 5 rats from each group sacrificed and; heart and thoracic aorta tissues removed for both light microscopic and electron microscopic examinations. Results: Light microscopic examinations revealed that the endocardial thickness of all study groups was significantly different at 6 th and 16 th week of RT (p < 0.001 for both). Pair-wise comparisons showed that the differences were significant in IR-Hal (2.5)/IR (p < 0.001); IR-Hal (5.0)/IR (p < 0.001); and Hal (2.5)/IR-Hal (5.0)/IR (p = 0.001) at 16 th week of RT. There were significant differences within the study groups regarding to the thoracic aorta fibrosis scores only at 16 th week of RT (p = 0.002). Electron microscopic examinations demonstrated that there were significant differences between all the groups with respect to heart mitochondria scores at both 6 th week and 16 th weeks of RT (p < 0.001 for both). The differences between Hal (2.5)/IR and Hal (5.0)/IR with respect to the heart mitochondria scores were significant only at 16 th week of RT (p = 0.001). Conclusion: These data demonstrated that Halofuginone may improve radiation-induced cardiovascular injury. The most prominent improvement was observed in higher dose of Halofuginone group after long term follow-up.

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“…The senior author worked on experimental composite allotransplantation and permanent immunotolerance using different therapeutic methods. 3 The aim of our experimental studies is to achieve permanent immune tolerance without the use of immunosuppressive drugs and develop novel clinical composite tissue allotransplantations in the future. 4,5 Nerve allotransplantations in replanted arms have been performed by the authors on 2 children, the younger of whom had total motor and sensorial recovery.…”

Section: Discussionmentioning

confidence: 99%

“…Based on the promising results of an experimental study performed by our radiation oncology team, which points to the advantage of preoperative irradiation to reduce the antigenic load of the transplanted extremities, 3 we irradiated the extremities preoperatively.…”

Section: Irradiation Of the Procured Extremitiesmentioning

confidence: 99%

Lessons Learned From the First Quadruple Extremity Transplantation in the World

Nasır¹,

Kilic²,

Karaaltın³

et al. 2014

Annals of Plastic Surgery

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Concomitant trastuzumab with thoracic radiotherapy: a morphological and functional study

Abstract: T and high-dose RT may lead to vascular damage that seems at least additive.

Cited by 14 publications

References 32 publications

The effects of hormonotherapy administered concurrent radiotherapy and trastuzumab on cardiac toxicity in rats

The effects of hormonotherapy administered concurrent radiotherapy and trastuzumab on cardiac toxicity in rats

The effect of halofuginone on radiation-induced cardiovascular injury

Lessons Learned From the First Quadruple Extremity Transplantation in the World

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